1. Field of the Invention
This invention resides in the field of nanocrystalline materials and processes for their manufacture.
2. Description of the Prior Art
Quantum-sized particles, i.e., those having diameters within the range of about 0.1 nm to about 50 nm, also known as quantum dots or nanocrystals, are known for the unique properties that they possess as a result of both their small size and their high surface area. Some of these particles have unique magnetic properties that make the particles useful in ferro fluids, in magnetic tagging elements, and in electronic data systems such as recording media. Luminescent nanocrystals are particularly useful as detectable labels such as oligonucleotide tags, tissue imaging stains, protein expression probes, and the like, in applications such as the detection of biological compounds both in vitro and in vivo. Luminescent nanocrystals offer several advantages over conventional fluorophores, particularly for multiplexed and/or high sensitivity labeling. Nanocrystals typically have larger absorption cross sections than comparable organic dyes, higher quantum yields, better chemical and photochemical stability, narrower and more symmetric emission spectra, and a larger Stokes shift. Furthermore, the absorption and emission properties vary with the particle size and can be systematically tailored.
A variety of methods have been reported for the preparation of nanocrystals. These methods include inverse micelle preparations, arrested precipitation, aerosol processes, and sol-gel processes. A method commonly used for the preparation of binary nanocrystals is one in which an organometallic and elemental set of nanocrystal precursors is injected into a hot solvent as the solvent is being stirred. Product nucleation can begin immediately, but the injection causes a drop in the solvent temperature, which tends to halt the nucleation process. Nucleation and particle growth can be continued by heating the reaction mixture with further stirring, and the temperature can be dropped to stop the reaction when the desired particle size is obtained. As a result, the success of this batchwise xe2x80x9cstirred-potxe2x80x9d method is strongly affected by system parameters such as the initial temperature of the solvent, the injection temperature and in particular the injection rate, the stirring efficiency, the concentrations of the reactant materials, the length of time that the mixture is held at the reaction temperature, and the efficiency of the cooling both after injection and after the desired endpoint is achieved. Some of these parameters are difficult to control with precision, and this can lead to poor reproducibility of the product. The lack of precise control also leads to nanocrystals with surfaces that are nonuniform, products that are readily degradable, and/or nanocrystals with low emission quantum yields.
The initial reaction conditions, i.e., the manner and conditions under which the reaction is initiated, are particularly important in controlling the quality and uniformity of the product, far more so than in other types of synthesis. Stirred-pot methods suffer in this regard since there are limits to how rapidly and uniformly the temperature of the reaction mixture can be changed or otherwise controlled. The temperature drop that occurs upon injection of the precursors will vary with the precursor temperature prior to injection, the volume of precursor injected and its rate of injection, the volume of the heated solvent, and the stirring efficiency. The difficulty in cooling rapidly when terminating the reaction often means that a lower reaction temperature must be used as a means of avoiding excess reaction. Further difficulties with stirred-pot methods are that they often involve the injection of large volumes of flammable or pyrophoric materials at very high temperatures, or the rapid evolution of gases, all of which present safety hazards.
Control of the properties of nanocrystals by the application of coatings or shells has been reported, notably in International Patent Publication No. WO 99/26299 (PCT/US98/23984), xe2x80x9cHighly Luminescent Color-Selective Materials,xe2x80x9d Massachusetts Institute of Technology, applicant, international publication date May 27, 1999, and references cited therein. The application of an inorganic shell, for example, can increase the quantum yield of the nanocrystal as well its chemical stability and photostability. The techniques for applying a shell are stirred-pot techniques that are usually similar to those used for the preparation of the core. Like the diameter of the core, the thickness of the shell affects the properties of the finished product, and the thickness will vary with the same system parameters that affect the core. The difficulties in controlling these parameters in a stirred-pot system lead to difficulties in controlling the nature and quality of the final product.
The limitations and difficulties described above and others encountered in the preparation of nanocrystals are addressed by the present invention, which resides in processes and apparatus for the production of monodisperse luminescent semiconductor nanocrystals, for the application of a coating to nanocrystal cores, and for both. The manufacture of nanocrystals in accordance with this invention is accomplished by first dissolving or dispersing precursor materials capable of reacting to form nanocrystals in a solvent, for example a coordinating solvent, and introducing the resulting reaction mixture into a reaction tube that is embedded or immersed in a heat transfer medium. Likewise, the application of a coating to nanocrystal cores in accordance with this invention is accomplished by dispersing the nanocrystal cores in a solvent, for example a coordinating solvent, in which are dissolved the precursor materials for the coating, and introducing this reaction mixture into the reaction tube. In either case, the heat transfer medium maintains the reaction mixture at the desired reaction temperature, and the reaction mixture is passed continuously through the tube. The internal diameter of the tube is preferably small enough to promote rapid transfer of heat from the tube walls to the center of the fluid stream flowing through the tube and hence rapid heating of the continuously flowing stream to the reaction temperature. In addition to the tube diameter, the flow rate is varied and adjusted, and the tube length selected, to permit control of the reaction. Flow rate, temperature and pressure are all controllable, and in preferred embodiments the reaction is quenched by cooling the product stream upon its emergence from the reaction tube by any of various conventional cooling techniques.
Characteristic properties of the product stream, such as optical properties, electrical properties, magnetic properties, electromagnetic properties, and the like are detected and a comparison is made between the detected values and a predetermined or preselected target range that is indicative of the product quality sought to be achieved. Any discrepancy or deviation between the detected values and target range can then be used to adjust the variable reaction conditions, such as the temperature of the heat transfer medium, the flow rate of the reaction mixture through the tube, or both, until the product changes sufficiently that the detected values fall within or otherwise conform to the target range.
It has further been discovered that the final nanoparticle size, size distribution and yield can be controlled by introducing a reaction promoter into the reaction system under selected conditions such as exposure time and temperature. An example of a reaction promoter is air or generally any oxygen-containing gas (i.e., oxygen gas itself or a gas mixture containing molecular oxygen). The particle size, size distribution and yield affect the properties of the product stream listed above, i.e., the optical, electrical, magnetic, and electromagnetic properties, and deviations between the detected values and the target range can be reduced or eliminated by adjustment of the exposure time to the oxygen-containing gas, the temperature maintained during the exposure, or other characteristics of the exposure that can be varied. Exposure of the reaction mixture to the gas can be done before the reaction mixture enters the continuous-flow system or while the reaction mixture is in the continuous-flow system.
Reaction apparatus in accordance with this invention includes a thermally conductive reaction tube of sufficiently small internal diameter to accomplish effective heat transfer in the flowing stream, a heat transfer medium in thermal contact with the exterior of the reaction tube, a pump or other fluid-driving component for continuously supplying pressure to a reactant or precursor mixture to the reaction tube, a monitoring unit to evaluate, measure, or otherwise detect the properties of the product stream, preferably but not necessarily as the product stream leaves the reaction tube, as an indication of the nature and quality of the nanocrystals formed in the reaction mixture during its passage through the reaction tube, and optionally a control loop to adjust the reaction conditions in the tube or upstream of the tube to correct for any discrepances between the detected values and the target range.
Further details of these features and the various preferred embodiments of the several aspects of this invention are described below.